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<p>Immunotherapies aimed at enhancing anti-cancer immunity are now in wide clinical use. For instance, anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) therapy has demonstrated clinical efficacy in many tumor types, but overall, only a minority of patients respond. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that selectively destroys targeted cells. CD25-targeted NIR-PIT is a strategy that selectively depletes regulatory T cells in the tumor microenvironment, thereby enhancing the T-cell response of PD-1 mAbs. Cytokines, such as interleukin-15 (IL-15), can also modulate immune response by further activating CD8<sup>+</sup> T cells, thereby creating favorable CD8<sup>+</sup>/Treg ratio.</p><p>In this study, we evaluated the combination of CD25-targeted NIR-PIT and intratumoral IL-15 administration with anti-PD-1 mAb in treating syngeneic murine tumor models. The combination of CD25-targeted NIR-PIT and intratumoral IL-15 with anti-PD-1 mAb suppressed tumor growth, prolonged survival and increased the CD8<sup>+</sup>/Treg ratio. This combination achieved dramatic tumor control with 90% complete response and long-term survival, particularly in highly-immunogenic tumors. In addition, mice that achieved complete response resisted tumor re-inoculation suggesting durable memory T-cells were formed. In conclusion, the combination of CD25-targeted NIR-PIT and intratumoral IL-15 with anti-PD-1 therapy is a potentially useful strategy to improve the efficacy of immunotherapy.</p>

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Combined CD25-targeted near infrared photoimmunotherapy (NIR-PIT) and intratumor IL-15 enhance the effectiveness of anti-PD-1 immunotherapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月18日

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  • Makoto Kano,
  • Aki Furusawa,
  • Hiroshi Fukushima,
  • Seiichiro Takao,
  • Shuhei Okuyama,
  • Hiroshi Yamamoto,
  • Motofumi Suzuki,
  • Miyu Kano,
  • Ko Kitamura,
  • Peter L. Choyke,
  • Hisataka Kobayashi

摘要

Immunotherapies aimed at enhancing anti-cancer immunity are now in wide clinical use. For instance, anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) therapy has demonstrated clinical efficacy in many tumor types, but overall, only a minority of patients respond. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that selectively destroys targeted cells. CD25-targeted NIR-PIT is a strategy that selectively depletes regulatory T cells in the tumor microenvironment, thereby enhancing the T-cell response of PD-1 mAbs. Cytokines, such as interleukin-15 (IL-15), can also modulate immune response by further activating CD8+ T cells, thereby creating favorable CD8+/Treg ratio.

In this study, we evaluated the combination of CD25-targeted NIR-PIT and intratumoral IL-15 administration with anti-PD-1 mAb in treating syngeneic murine tumor models. The combination of CD25-targeted NIR-PIT and intratumoral IL-15 with anti-PD-1 mAb suppressed tumor growth, prolonged survival and increased the CD8+/Treg ratio. This combination achieved dramatic tumor control with 90% complete response and long-term survival, particularly in highly-immunogenic tumors. In addition, mice that achieved complete response resisted tumor re-inoculation suggesting durable memory T-cells were formed. In conclusion, the combination of CD25-targeted NIR-PIT and intratumoral IL-15 with anti-PD-1 therapy is a potentially useful strategy to improve the efficacy of immunotherapy.